Induction of matrix metalloproteinase-1 (MMP-1) during epidermal invasion of the stroma in human skin organ culture: keratinocyte stimulation of fibroblast MMP-1 production.

摘要: Organ cultures of human skin were incubated for 8 days under growth factor-free conditions or exposed to 10 ng ml(-1) recombinant epidermal factor (EGF) during the incubation period. Normal histological features preserved in absence factor, while epithelial cells underwent a proliferative response and invaded underlying stroma presence exogenous EGF. The same concentrations EGF that induced stromal invasion also resulted up-regulation matrix metalloproteinase-9 (MMP-9; 92-kD gelatinase B) organ culture keratinocyte monolayer culture, expression MMP-1 (interstitial collagenase) fibroblast culture. When potent, irreversible EGF-receptor tyrosine kinase (EGF-RTK) antagonist along with EGF, abnormal reversed, MMP-9 production was suppressed. In contrast, EGF-RKT antagonism had only modest inhibitory effect on production. Culture fluid from keratinocytes grown stimulated proliferation elaboration. Treatment fibroblasts EGF-RTK inhibited keratinocyte-induced but (approximately 20% inhibition) treatment dermal Interleukin-1 Receptor Antagonist no strongly (greater than 70% inhibition). These data indicate by EGF-treated is associated events occurring both epidermis dermis. direct appears be primarily epidermis. Dermal reflect, at least part, factors elaborated